Cold-Induced Thermogenesis Depends on ATGL-Mediated Lipolysis in Cardiac Muscle, but Not Brown Adipose Tissue.,Cell Metabolism

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Cold-Induced Thermogenesis Depends on ATGL-Mediated Lipolysis in Cardiac Muscle, but Not Brown Adipose Tissue.
Cell Metabolism ( IF 27.7 ) Pub Date : 2017-Nov-07 , DOI: 10.1016/j.cmet.2017.09.004
Renate Schreiber ₁ , Clemens Diwoky ₁ , Gabriele Schoiswohl ₁ , Ursula Feiler ₁ , Nuttaporn Wongsiriroj ₁ , Mahmoud Abdellatif ₂ , Dagmar Kolb ₃ , Joris Hoeks ₄ , Erin E Kershaw ₅ , Simon Sedej ₆ , Patrick Schrauwen ₄ , Guenter Haemmerle ₇ , Rudolf Zechner ₇

Affiliation

Fatty acids (FAs) activate and fuel UCP1-mediated non-shivering thermogenesis (NST) in brown adipose tissue (BAT). Release of FAs from intracellular fat stores by adipose triglyceride lipase (ATGL) is considered a key step in NST. Accordingly, the severe cold intolerance of global ATGL knockout (AKO) mice has been attributed to defective BAT lipolysis. Here we show that this conclusion is incorrect. We demonstrate that although the BAT-specific loss of ATGL impairs BAT lipolysis and alters BAT morphology, it does not compromise the β₃-adrenergic thermogenic response or cold-induced NST. Instead, NST depends on nutrient supply or lipolysis in white adipose tissue during fasting, suggesting that circulating energy substrates are sufficient to fuel NST. Cold intolerance in AKO mice is not caused by BAT dysfunction as previously suspected but by severe cardiomyopathy. We conclude that functional NST requires adequate substrate supply and cardiac function, but does not depend on ATGL-mediated lipolysis in BAT.

中文翻译：

冷诱导产热取决于心脏肌肉中 ATGL 介导的脂肪分解，而不是棕色脂肪组织。

脂肪酸 (FA) 在棕色脂肪组织 (BAT) 中激活并促进 UCP1 介导的非颤抖产热 (NST)。脂肪甘油三酯脂肪酶 (ATGL) 从细胞内脂肪储存中释放 FA 被认为是 NST 的关键步骤。因此，全球 ATGL 基因敲除 (AKO) 小鼠的严重冷不耐受归因于 BAT 脂解缺陷。这里我们证明这个结论是不正确的。我们证明，虽然 BAT 特异性的 ATGL 损失会损害 BAT 脂肪分解并改变 BAT 形态，但它不会损害 β ₃-肾上腺素能产热反应或冷诱导的 NST。相反，NST 取决于禁食期间白色脂肪组织的营养供应或脂肪分解，这表明循环能量底物足以为 NST 提供燃料。AKO 小鼠的冷不耐受不是由先前怀疑的 BAT 功能障碍引起的，而是由严重的心肌病引起的。我们得出结论，功能性 NST 需要足够的底物供应和心脏功能，但不依赖于 ATGL 介导的 BAT 脂肪分解。

更新日期：2017-10-05

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